Several naturally-occurring dimeric alkaloids obtainable from Vinca rosea have been found active in the treatment of experimental malignancies in animals. Among these are leurosine (U.S. Pat. No. 3,370,057), vincaleukoblastine (vinblastine or VLB) (U.S. Pat. No. 3,097,137), leurosidine (vinrosidine) and leurocristine (VCR or vincristine) (both in U.S. Pat. No. 3,205,220). Two of these alkaloids, VLB and vincristine, are now marketed as drugs for the treatment of malignancies, particularly the leukemias and related diseases in humans. Vinblastine and vincristine can be represented by Formula I below which also illustrates the conventual numbering system for the dimeric indole alkaloids. ##STR1## When R is methyl in Formula I, the compound is vinblastine and when R is formyl, the compound is vincristine.
In the Formula I compounds, the lower ring is usually referred to as the vindoline moiety, in that vinblastine is a 15-substituted vindoline and vincristine is a 15-substituted derivative of a modified (1-formyl rather than 1-methyl) vindoline. N-desmethylvinblastine (1-desmethylvinblastine) or desformylvincristine is also a 15-substituted modified vindoline. The compound is described in U.S. Pat. No. 3,354,163.
U.S. Pat. No. 3,422,112 describes the preparation of 15-substituted vindolines by the reaction of vindoline with various indole derivatives including perivinol, 18-hydroxy dihydrocleavamine, 18-hydroxyibogamine, vobasinol and the like.
The fermentation of vindoline with S. albogriseolus to produce other metabolites has been reported by Mallet et al. in the abstracts of the 151st meeting of the American Chemical Society fall 1967 at Pittsburgh, Pa.
N-desmethyl (1-desmethyl) vindoline has not hitherto been described.